On the Reactivity of (S)-Indoline-2-Carboxylic Acid.

(S)-Indoline-2-carboxylic acid (H-(2S)-Ind-OH) possesses the ability to influence the conformation of peptide bonds towards the cis amide isomer in polar solvents. However, its potential utilization as a conformational switch within long peptide sequences poses challenges due to its low reactivity and strong inclination to form diketopiperazines. The present study explores its reactivity under various conditions and proposes synthetic strategies to overcome these limitations. A series of H-(2S)-Ind-OH containing di- and tri-peptides have been efficiently synthesized and characterized, ready to be inserted in more complex and longer sequences.